Mechanical Index Impulses Research Articles

Clinical trials of sonothrombolysis for Acute Coronary Syndromes

Diagnostic high mechanical index (MI) ultrasound in conjunction with microbubble infusion in patients with acute ST-elevation myocardial infarction (STEMI) may be a method of achieving early recanalization, (sonothrombolysis). To evaluate the safety, efficacy and prognostic impact of sonothrombolysis in patients with acute coronary syndromes (ACS). We will randomize 540 patients with anterior STEMI in the “High Ultrasound Mechanical Index and MicrobuBBLEs to reduce acute myocardial infarction burden” (HUBBLE-I). Sonothrombolysis (50 min) was performed using multiple intermittent high MI impulses when microbubbles were imaged within the risk area (Therapy Group) or only 3 projections of low MI imaging alone plus microbubbles (Control Group) in 5 patient subgroups: G1-STEMI pre-PCI; G2-STEMI after lytic therapy; G3-Unstable angina and non-STEMI; G4-STEMI post-PCI; G5-STEMI pre-PCI treated in ambulances. Recanalization, ejection fraction, troponin and MB-CK levels were acquired at baseline, pre-PCI and follow-up. Global longitudinal strain was serially measured. The number of patients randomized to control versus therapy was 47(23/24), as follows: G1- 12 (5/7); G2- 13 (9/4); G3- 14 (8/6); G4- 8 (4/4) and G5- 0(0/0). This multicenter, Phase III randomized trial in patients with ACS treated by sonothrombolysis will assess safety, efficacy, and prognostic impact of this therapy.

Abstract 14082: The Effect of Diagnostic Ultrasound Mediated High Mechanical Impulses on Cardiac Output During an Ultrasound Enhancing Agent Infusion

Introduction: Diagnostic ultrasound high mechanical index (MI) impulses are used during an ultrasound enhancing agent (UEA) infusion to improve endocardial border resolution and study myocardial perfusion. They have also been shown to cause endothelial shear, resulting in prolonged increases in ATP release and augment microvascular flow. The potential for these high MI impulses to alter cardiac output (CO) are unknown. Hypothesis: To study the impact of high MI impulses on CO Methods: Fifty one patients (mean age 63±15 years; 41% female) referred for contrast echocardiography underwent very low MI imaging with intermittent high MI impulses (1.6-1.7 Megahertz) in three different apical windows during either a Definity (Lantheus Medical) or Lumason (Bracco Diagnostics) infusion or bolus. CO was determined from Doppler measurements of left ventricular outflow tract stroke volume and heart rate. Mean contrast enhanced biplane left ventricular ejection fraction (LVEF) was 53±15%; (range 10-75%). CO from baseline without contrast (COwoC) and baseline after contrast (COwC) before high MI impulses were compared to CO after contrast and after high MI impulses (COaHMI). All CO measurements were made by an independent reviewer blinded to time of measurement (before or after high MI impulses). Results: Although heart rate did not change before and after intermittent high MI impulse administration, COaHMI increased significantly when compared to COwoC and COwC (p< 0.001 for both comparisons; Figure). In nine patients (18%), CO increased by more than 20%. In patients with LVEF < 40% COwC was 2.4±0.8 liters per minute (LPM) and COaHMI increased to 2.7± 0.8 LPM (p=0001). In patients with LVEF≥40%, COwC was 3.4±1.06 LPM while COaHMI increased to 3.8± 1.2 LPM (p=0.00001). Conclusions: Application of diagnostic guided high MI impulses during a commercially available microbubble infusion significantly increases CO irrespective of underlying left ventricular systolic function.

EFFECT OF DIAGNOSTIC INTERMITTENT HIGH MECHANICAL INDEX IMPULSES DURING AN ULTRASOUND ENHANCING AGENT INFUSION ON GLOBAL AND REGIONAL LONGITUDINAL STRAIN IN PATIENTS WITH ABNORMAL SYSTOLIC FUNCTION

Intermittent high (IH) mechanical index (MI) impulses during transthoracic ultrasound are recommended during very low MI (VLMI) imaging for improving endocardial border delineation following an intravenous injection or infusion of ultrasound enhancing agents (UEAs). These high MI impulses have also

Sonothrombolysis in ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention

BackgroundPreclinical studies have demonstrated that high mechanical index (MI) impulses from a diagnostic ultrasound transducer during an intravenous microbubble infusion (sonothrombolysis) can restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI). ObjectivesThis study tested the clinical effectiveness of sonothrombolysis in patients with STEMI. MethodsPatients with their first STEMI were prospectively randomized to either diagnostic ultrasound–guided high MI impulses during an intravenous Definity (Lantheus Medical Imaging, North Billerica, Massachusetts) infusion before, and following, emergent percutaneous coronary intervention (PCI), or to a control group that received PCI only (n = 50 in each group). A reference first STEMI group (n = 203) who arrived outside the randomization window was also analyzed. Angiographic recanalization before PCI, ST-segment resolution, infarct size by magnetic resonance imaging, and systolic function (LVEF) at 6 months were compared. ResultsST-segment resolution occurred in 16 (32%) high MI PCI versus 2 (4%) PCI-only patients before PCI, and angiographic recanalization was 48% in high MI/PCI versus 20% in PCI only and 21% in the reference group (p < 0.001). Infarct size was reduced (29 ± 22 g high MI/PCI vs. 40 ± 20 g PCI only; p = 0.026). LVEF was not different between groups before treatment (44 ± 11% vs. 43 ± 10%), but increased immediately after PCI in the high MI/PCI group (p = 0.03), and remained higher at 6 months (p = 0.015). Need for implantable defibrillator (LVEF ≤30%) was reduced in the high MI/PCI group (5% vs. 18% PCI only; p = 0.045). ConclusionsSonothrombolysis added to PCI improves recanalization rates and reduces infarct size, resulting in sustained improvements in systolic function after STEMI. (Therapeutic Use of Ultrasound in Acute Coronary Artery Disease; NCT02410330).

EFFECT OF DIAGNOSTIC INTERMITTENT HIGH MECHANICAL INDEX IMPULSES ON GLOBAL LONGITUDINAL STRAIN IN PATIENTS BEING EVALUATED FOR SIGNIFICANT CORONARY ARTERY DISEASE

Intermittent high (IH) mechanical index (MI) impulses from a transcutaneous diagnostic transducer are used to improve endocardial border delineation and analyze myocardial perfusion during infusion of ultrasound enhancing agents (UEAs) These high MI impulses have also been shown to augment skeletal

Utilization of modified diagnostic ultrasound and microbubbles to reduce myocardial infarct size

ObjectiveWe sought to determine whether guided high mechanical index (MI) impulses from a diagnostic ultrasound transducer during an intravenous microbubble infusion could augment low-dose fibrinolytic therapy in treating acute myocardial...

Abstract 9845: Efficacy and Safety of Transcranial Ultrasound and Microbubbles in Treating Acute Ischemic Stroke Without Thrombolytic Agents

Background. Although transcranial ultrasound (TCUS) and microbubbles (MB) have been utilized in the emergent management of stroke, it remains unclear what TCUS parameters are required to be effective. Furthermore, it is unclear whether TCUS alone, without supplemental thrombolytic agents, could produce thrombolysis without intracranial hemmorhage (ICH). The purpose of this study was to determine whether TCUS pulse sequences which elicit predominately inertial cavitation (IC) versus stable cavitation (SC) of MB would be more effective in recanalizing the cerebral vessels in acute stroke. Methods. In 24 pigs, three hour old venous thrombi were embolized into the internal carotid and middle cerebral arteries. After angiographic documentation of persistent bilateral occlusion, pigs were randomized to a continuous infusion of MB using intravenous 3% Definity, during which either guided high mechanical index (MI) impulses (2.3 MI; 5 usec pulse duration) or guided intermediate MI impulses (1.7 MI, 20 usec pulse duration) were administered. The impulses were applied only when simultaneous low MI imaging detected MB within the cortex. A third control group received high MI impulses (2.3 MI) alone without MB. All pigs received aspirin. Radiofrequency (RF) data was collected from returning signals in all pigs to determine whether noise based IC or ultraharmonic based SC were created. Microscopic analysis (Hematoxylin/Eosin) was performed to analyze for ICH post-mortem. Results. Attenuation across the pig skull (measured ex vivo) using a calibrated hydrophone was &gt;52% in all pigs. Recanalization rates were highest for guided high MI impulses in the presence of MB (8/8 versus 3/8 for guided intermediate MI impulses/MB and 4/8 for high MI TCUS alone; p&lt;0.05). Although the intermediate MI impulses created both SC and IC, a more homogenous IC field was created with guided high MI impulses in the presence of MB. Microscopic analysis of ipsilateral and contralateral cortex indicated no ICH in any pig. Conclusions. TCUS and intravenous commercially available MB are capable of safely restoring cerebral blood flow without the need for thrombolytic agents. Achieving a dominant IC field appears critical to produce thrombolysis.